Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization
Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization
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DOI：
10.1016/j.ydbio.2006.05.038
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发表时间：
2006-08-15
影响因子：
2.7
通讯作者：
Conti, Marco
中科院分区：
文献类型：
--
作者：
Xie, Fang;Garcia, Manuel A.;Conti, Marco
We previously demonstrated that male mice deficient in the soluble adenylyl cyclase (sAC) are sterile and produce spermatozoa with deficits in progressive motility and are unable to fertilize zona-intact eggs. Here, analyses of sAC(-/-) spermatozoa provide additional insights into the functions linked to cAMP signaling. Adenylyl cyclase activity and cAMP content are greatly diminished in crude preparations of sAC(-/-)spermatozoa and are undetectable after sperm purification. HCO3- is unable to rapidly accelerate the flagellar beat or facilitate evoked Ca2+ entry into sAC(-/-) spermatozoa. Moreover, the delayed HCO3--dependent increases in protein tyrosine phosphorylation and hyperactivated motility, which occur late in capacitation of wild-type spermatozoa, do not develop in sAC(-/-) spermatozoa. However, sAC(-/-) sperm fertilize zona-free oocytes, indicating that gamete fusion does not require sAC. Although ATP levels are significantly reduced in sAC(-/-) sperm, cAMP-AM ester increases flagellar beat frequency, progressive motility, and alters the pattern of tyrosine phosphorylated proteins. These results indicate that sAC and cAMP coordinate cellular energy balance in wild-type sperm and that the ATP generating machinery is not operating normally in sAC(-/-)spermatozoa. These findings demonstrate that sAC plays a critical role in cAMP signaling in spermatozoa and that defective cAMP production prevents engagement of multiple components of capacitation resulting in male infertility. (c) 2006 Elsevier Inc. All rights reserved.
